Many cellular processes require large-scale rearrangements of chromatin structure. Structural maintenance of chromosomes (SMC) protein complexes are molecular machines that can provide structure to chromatin. These complexes can connect DNA elements in cis, walk along DNA, build and processively enlarge DNA loops and connect DNA molecules in trans to hold together the sister chromatids. These DNA-shaping abilities place SMC complexes at the heart of many DNA-based processes, including chromosome segregation in mitosis, transcription control and DNA replication, repair and recombination. In this Review, we discuss the latest insights into how SMC complexes such as cohesin, condensin and the SMC5–SMC6 complex shape DNA to direct these fundamental chromosomal processes. We also consider how SMC complexes, by building chromatin loops, can counteract the natural tendency of alike chromatin regions to cluster. SMC complexes thus control nuclear organization by participating in a molecular tug of war that determines the architecture of our genome.
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Owing to space limitations, the authors apologize for not being able to cite all relevant articles or discuss all aspects of SMC biology. The authors acknowledge financial support from the European Research Council (772471-CohesinLooping) and from the Dutch Research Council (VI.C.202.098) and thank A. Friskes and members of the Rowland Laboratory for critical reading of the manuscript.
The authors declare no competing interests.
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A molecular linkage that naturally arises in processes such as DNA replication, in which two DNA molecules are knotted in such a way that can only be resolved by the breaking of the DNA chain.
An accumulation of different heterochromatin regions into a dense structure within the nuclei of some types of animal cells.
A chromatin-organizing protein that binds to a specific DNA motif and acts as a boundary for extruding cohesin complexes.
A chromatin conformation capture technique, in which regions that are close together in the nucleus are crosslinked and identified by sequencing, which provides genome-wide information about the 3D nuclear architecture of a population of cells.
- Malformation syndromes
A disorder characterized by congenital anomalies that are causally related.
- Promyelocytic leukaemia bodies
Nuclear membrane-less organelles that accumulate certain proteins and that have been implicated in processes ranging from DNA damage repair to antiviral defence.
- Topologically associating domains
(TADs). Self-interacting genomic regions as observed by chromatin capture techniques that are flanked by CTCF binding sites and consist of chromatin loops formed by cohesin.
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Hoencamp, C., Rowland, B.D. Genome control by SMC complexes. Nat Rev Mol Cell Biol (2023). https://doi.org/10.1038/s41580-023-00609-8